CELF6

Chr 15

CUGBP Elav-like family member 6

Also known as: BRUNOL6

NCBI Gene: 60677 ENSG00000140488 UniProt: Q96J87 OMIM: 612681

Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.004

Z-score 2.81

OE 0.36 (0.21–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.56Z-score

OE missense 0.57 (0.50–0.65)

163 obs / 284.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.65)

0≤0.351.4

Missense OE?0.57 (0.50–0.65)

0≤0.61.4

Synonymous OE?0.74

0≤1.21.6

LoF obs/exp: 8 / 22.4Missense obs/exp: 163 / 284.4Syn Z: 2.32

Background carrier burden — how many people carry a rare variant somewhere in CELF6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

602 rare PASS variants

Rare truncating (LoF)

1 in 2,400

83 rare PASS variants

Rare synonymous (reference)

1 in 220

308 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CELF6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 2,800
South Asian	~43k	1 in 130	1 in 620
Remaining (unassigned)	~30k	1 in 140	1 in 2,000
European (Finnish)	~27k	1 in 450	1 in 4,000
Admixed American	~22k	1 in 200	1 in 1,300
African / African American	~21k	1 in 110	1 in 1,800
East Asian	~20k	1 in 210	1 in 950
Ashkenazi Jewish	~13k	1 in 960	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 12 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 12.? see exons ↓